瑞戈非尼结晶工艺研究  

Crystallization Process Study of Regorafenib

作　　者：李宏名 张娇 LI Hongming;ZHANG Jiao(Sinopharm Chuankang Pharmaceutical Co.,Ltd.,Chengdu 611731,China;Sichuan Kelun Pharmaceutical Research Institute Co.,Ltd.,Chengdu 611138,China)

机构地区：[1]国药集团川抗制药有限公司,成都611731 [2]四川科伦药物研究院有限公司,成都611138

出　　处：《中国现代应用药学》2025年第5期754-759,共6页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的优化瑞戈非尼结晶工艺,以控制基因毒性杂质含量。方法测定粗品在不同溶剂中的溶解度以及不同溶剂中基因毒性杂质的增长情况,确定结晶溶剂体系和结晶方式;采用悬浮转晶试验和FBRM在线监测结晶过程确定目标晶型的结晶工艺条件;采用研磨的方式研究择优取向;采用考察养晶过程中的液相浓度变化和固相形貌变化来控制养晶时间。结果确定了瑞戈非尼FormⅠ晶型的结晶工艺。结论优化后的结晶工艺产品中基因毒性杂质含量低,晶型纯度高,工艺参数易于控制,适宜工业化生产。OBJECTIVE To optimize crystallization process of regorafenib to control the content of genotoxic impurities.METHODS The solubility of the crude product and the increase of genotoxic impurities in different solvents were determined to identify the crystallization solvent system and crystallization mode.Suspension transformation experiments and FBRM online monitoring were used to determine the crystallization process conditions for the target crystal form.Grinding was employed to study preferred orientation.The changes in liquid phase concentration and solid phase morphology during crystal maturation were investigated to control the ripening time.RESULTS The crystallization process for Regorafenib FormⅠhad been established.CONCLUSION The optimized crystallization process yields a product with low genotoxic impurity content,high crystal form purity,and easily controllable process parameters,making it suitable for industrial production.

关 键 词：瑞戈非尼 基因毒性杂质 择优取向 悬浮转晶试验 养晶时间 

分 类 号：R914.4[医药卫生—药物化学]